Over January 24th/25th, the US Tobacco Products Scientific Advisory Committee (TPSAC) sat in session to consider PMI’s Modified Risk Tobacco Product Application (MRTPA) for the heated tobacco product IQOS. In preparation for the meeting, the FDA produced its own briefing document in which the top banana regulatory body acknowledged that:
- The process of heating rather than burning tobacco results in significantly reduced levels of toxin release
- IQOS was likely to be acceptable to current smokers while, for a number of reasons, be unappealing to non-smokers.
So far so good. The FDA also asked a set of questions that it wished the TPSAC to consider and vote on. There were some highly subjective questions asking the committee to grade high/medium/low ‘ the ‘likelihood’ of the appeal of IQOS to non-smokers and young people, incidence of complete switching or long-term dual use. But the key questions focussed on reduced exposure to harmful chemicals and the likely impact on health. The outcome of the voting on the issue of risk reduction needs a certain amount of unpacking.
They voted 8-1 in favour of the FDA proposition that users of IQOS would be exposed to significantly lower levels of toxins than smokers, yet nobody voted ‘yes’ that having been exposed to much reduced levels of toxins, this can (note: not will ) reduce the risk of tobacco-related diseases and they also voted against the proposition that a complete switch from cigarettes to IQOS would translate to “measurable and substantial reductions in morbidity and mortality”.
Now it is a reasonable point that if you reduce the level of toxins, that still leaves open how much exposure to the remaining level of toxins it takes to trigger a disease response. And it would be unlikely that long-term heavy smoker who switched could significantly undo the existing damage. Except I know one vaper who quit smoking aged 70 and improved lung function by about 30%, while Professor Polosa has demonstrated that e-cigarette users with respiratory problems and high blood who substantially reduced their cigarette consumption, have improvements in subjective and objective health outcomes that are similar to those reported in patients who remain completely abstinent after switching.
But remember the TPSAC refused to even accept that reduced risk of disease can happen. If you turn this on its head, it’s like going to the doctor and saying, “Look doctor, I’ve cut down from 40 a day to 2 day’ and the doctor turns round and says ‘So what?’. A new meta-analysis concludes that smoking one cigarette a day poses about half the heart disease and stroke risk of smoking 20 a day. It is still high, but the risk is still reduced.
As non-scientist, I can’t conceive of any kind of experiment except the most highly unethical (and maybe not even then) that could begin to answer the central question – with its key phrase ‘measurable and substantial’ - as it relates to the toxins in tobacco smoke. Which if correct, leads to the less magnanimous conclusion that this is the whole point: that no manufacturer, even with the seemingly limitless resources of PMI, could ever give a satisfactory answer to regulators.
It seems quite likely that other, less evidence-based forces are at work here. The first is that you have a group of clinicians who are on a government appointed body looking at a submission from a major tobacco company to allow the sale of a new tobacco-based product. Leaving aside the fear of innovation, getting a high five from peers for socking it to Big Tobacco will be a huge temptation however unscientific. Even without the weight of history behind such a submission, this type of advisory body will often take a very conservative and cautionary approach to their deliberations, not least because group dynamics kick-in which will serve to neutralise individual perhaps more radical views. The one thing a committee chair hates is the prospect of a minority report and s/he will do their utmost to push for a strong consensus.
But really, all of this is moot because it should now be a given that safer nicotine products not only represent a clear and present benefit now, but also, as far as anybody can reasonably ascertain, do not present any kind of danger for the future. And if at some point, unforeseen problems become apparent, that’s for the regulatory bodies to deal with at the time, hopefully with reference to a proportionate and pragmatic set of production standards - not for current advisory incumbents to try and deny smokers the chance to improve health and reduce the risk of death. Analysts believe that the chance of FDA approval are still good, but timing is less certain. For now, and I never thought I would be quoting Ronald Regan, but apparently he did say that “status quo is Latin for ‘mess we’re in”.
It has become almost a cliché to make constant reference to balanced and considered reports on e-cigarettes from Public Health England and the Royal College of Physicians. With the weight of the FDA, CDC, major American health charities and anti-tobacco campaigners (not to mention the primarily US-funded WHO), the chance of anything similar emerging from the States seemed remote.
So I am happy to report that in general, one can add the new report by the National Academy of Sciences to that very small pile of reports worth referencing. Nothing in this world is perfect of course, the Academy did stand firm on the ‘ substantial evidence’ of the gateway effect, and many of the more welcome conclusions are quite hedged, but even so:
- "There is substantial evidence that except for nicotine, under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes."
- "There is conclusive evidence that completely substituting e-cigarettes for combustible tobacco cigarettes reduces users’ exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes."
- "There is moderate evidence that risk and severity of dependence are lower for e-cigarettes than combustible tobacco cigarettes."
- "There is moderate evidence that second-hand exposure to nicotine and particulates is lower from e-cigarettes compared with combustible tobacco cigarettes."
- "There is no available evidence whether or not e-cigarette use is associated with clinical cardiovascular outcomes (coronary heart disease, stroke, and peripheral artery disease) and subclinical atherosclerosis (carotid intima media-thickness and coronary artery calcification)."
- "There is insufficient evidence that e-cigarette use is associated with long-term changes in heart rate, blood pressure, and cardiac geometry and function."
- "There is no available evidence whether or not e-cigarette use is associated with intermediate cancer endpoints in humans. This holds true for comparisons of e-cigarette use compared with combustible tobacco cigarettes and e-cigarette use compared with no use of tobacco products."
- "There is no available evidence whether or not e-cigarettes cause respiratory diseases in humans."
- "There is limited evidence for improvement in lung function and respiratory symptoms among adult smokers with asthma who switch to e-cigarettes completely or in part (dual use)."
- "There is limited evidence for reduction of chronic obstructive pulmonary disease (COPD) exacerbations among adult smokers with COPD who switch to e-cigarettes completely or in part (dual use)."
- "While the overall evidence from observational trials is mixed, there is moderate evidence from observational studies that more frequent use of e-cigarettes is associated with increased likelihood of cessation."
- "There is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults."
- "There is conclusive evidence that, other than nicotine, the number, quantity, and characteristics of potentially toxic substances emitted from e-cigarettes is highly variable and depends on product characteristics (including device and e-liquid characteristics) and how the device is operated."
Could this be a game-changer in terms, not only of US tobacco control politics, but more widely given the influence of the US on the global public health scene? And following on from Big Tobacco’s sackcloth and ashes advertising, will there be a US tobacco control ‘mea culpa’ for misleading the general public? Is it unlucky 13 for the anti-harm reduction lobby, or will they just cling on grimly to the ‘insubstantial’ evidence of the gateway effect?
See also Dr Michael Siegel’s blog commentary